Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis
- Design
- Randomized trial · 407 participants · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationMean BMI 40; weight loss is an established OA pain treatment. No normal-weight OA patients.
- Could weight loss explain it?
- LikelyPain relief is expected from 13.7% weight loss; the trial did not test weight-independent effects. Placebo group also improved substantially (-27.5).
- Study tier
- Study tier 2Adequately sized RCT with patient-reported endpoints; effect confounded with weight loss.
- Assessment
- Version 2 · curated · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
In 407 people with obesity (average BMI 40) and painful knee osteoarthritis, semaglutide produced 13.7% weight loss and greater pain reduction than placebo over 68 weeks. Because weight loss itself relieves knee pain, this does not show an anti-inflammatory or joint-specific drug effect, and it does not apply to people of normal weight.
01Findings
What the study reported
- Drugs
- Semaglutide
- Dose
- 2.4 mg once weekly
- Route
- subcutaneous
- Treatment duration
- 68 weeks
- Comparator
- placebo (both with diet/activity counselling)
- Primary outcome
- Percent change in body weight and change in WOMAC pain score at week 68
- Effect
- Weight -13.7% vs -3.2%; WOMAC pain -41.7 vs -27.5 points; SF-36 physical function +12.0 vs +6.5
- 95% confidence interval
- Not extracted
- P value
- <0.001
- Follow-up
- 68 weeks
- Adverse events
- Discontinuation due to adverse events 6.7% vs 3.0%, mostly GI; serious adverse events similar.
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Mean age
- 56
- Sex distribution
- 81.6% female
- Bmi mean
- 40.3
- Bmi min
- 30
- Obesity status
- obesity required; mean BMI 40.3
- Baseline condition
- moderate knee osteoarthritis with at least moderate pain
- Sample size
- 407
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 407
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo
- Follow up duration
- 56 years
- Outcome type
- patient-reported pain and function
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- not extracted
- Risk of bias
- not assessed (auto)
- Funding conflicts
- yes
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Novo Nordisk
- Industry funded
- Yes
- Manufacturer
- Novo Nordisk
- Sponsor role
- Sponsor designed and analysed.
- Author conflicts
- Authors report Novo Nordisk relationships; sponsor co-authors.
- Independent replication
- no
- Notes
- Authors declare relationships with the drug's manufacturer: Novo Nordisk
Funding is shown on every study and never used to score it.
03Claims
Claims this study bears on
- GLP-1 receptor agonists reduce osteoarthritis pain through mechanisms beyond weight loss.Mixed
STEP 9: WOMAC pain -41.7 vs -27.5; weight -13.7% vs -3.2%; mediation not tested.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Weight reduction has been shown to alleviate symptoms of osteoarthritis of the knee, including pain. The effect of glucagon-like peptide-1 receptor agonists on outcomes in knee osteoarthritis among persons with obesity has not been well studied. [METHODS] We conducted a 68-week, double-blind, randomized, placebo-controlled trial at 61 sites in 11 countries. Participants with obesity (a body-mass index [BMI; the weight in kilograms divided by the square of the height in meters] of ≥30) and a clinical and radiologic diagnosis of moderate knee osteoarthritis with at least moderate pain were randomly assigned, in a 2:1 ratio, to receive once-weekly subcutaneous semaglutide (2.4 mg) or placebo, in addition to counseling on physical activity and a reduced-calorie diet. The primary end points were the percentage change in body weight and the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (on a scale of 0 to 100, with higher scores reflecting worse outcomes) from baseline to week 68. A key confirmatory secondary end point was the physical-function score on the 36-Item Short Form Health Survey (SF-36), version 2 (on a scale of 0 to 100, with higher scores indicating greater well-being). [RESULTS] A total of 407 participants were enrolled. The mean age was 56 years, the mean BMI 40.3, and the mean WOMAC pain score 70.9. A total of 81.6% of the participants were women. The mean change in body weight from baseline to week 68 was -13.7% with semaglutide and -3.2% with placebo (P<0.001). The mean change in the WOMAC pain score at week 68 was -41.7 points with semaglutide and -27.5 points with placebo (P<0.001). Participants in the semaglutide group had a greater improvement in SF-36 physical-function score than those in the placebo group (mean change, 12.0 points vs. 6.5 points; P<0.001). The incidence of serious adverse events was similar in the two groups. Adverse events that led to permanent discontinuation of the trial regimen occurred in 6.7% of the participants in the semaglutide group and in 3.0% in the placebo group, with gastrointestinal disorders being the most common reason for discontinuation. [CONCLUSIONS] Among participants with obesity and knee osteoarthritis with moderate-to-severe pain, treatment with once-weekly injectable semaglutide resulted in significantly greater reductions in body weight and pain related to knee osteoarthritis than placebo. (Funded by Novo Nordisk; STEP 9 ClinicalTrials.gov number, NCT05064735.).
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 39476339 first ingestion |